Inside Health

BASICS; Job Description Grows For Our Utility Hormone

By NATALIE ANGIER

Published: May 3, 2011

Just when you thought that serotonin was pass?and you'd tossed all your half-used bottles of S.S.R.I.-type antidepressants because the ones that didn't give you nausea or smother your libido left you wondering whether you were in the placebo arm of a clinical trial, here comes a raft of new discoveries that sweeps the small, evolutionarily ancient and slyly powerful signaling molecule back on to center stage.

Researchers lately have learned that serotonin plays an impressive number of critical roles throughout the body, both below the neck and above it, and from the earliest days of prenatal pre-sentience. One team has found that serotonin starts seeping into the embryonic forebrain during the first trimester of pregnancy, helping to shape the basic neural circuitry that later in life will be applied to learning, emoting and consulting a psychiatrist.

More surprising still, Pat Levitt of the Zilkha Neurogenetic Institute at the University of Southern California and his colleagues reported in the April 21 issue of the journal Nature, the creator of all that architectonic prenatal serotonin turns out to be an organ long dismissed as a passive sieve: the placenta. Other researchers have determined that serotonin in the gut helps orchestrate the remodeling of bone, the lifelong buildup and breakdown of osteoclasts and osteoblasts that make the human skeleton such an exciting organ system to own.

The latest findings may never lead to a satisfying pharmacologic fix for what the psychiatrist Kay Redfield Jamison has called ''ordinary existential angst'' and others ''terminal you-ness,'' but they may someday help stiffen the spine, and they remind us that it's worth listening to serotonin no matter what it has to say.

''If I didn't admit to being surprised by the scope of serotonin function, and how important it is to tissues like bone,'' said Patricia Ducy, who studies the effect of serotonin on bone biology at Columbia University Medical Center, ''I would be lying.''

Serotonin is a tiny molecule, a bibelot built of just 10 carbon atoms, a dozen hydrogens, two nitrogens and a single oxygen. The molecule was first detected in 1948, in blood serum, and it was shown be a vascular toning agent that causes blood vessels to constrict -- hence its name, a conjoinment of ''serum'' and ''tone.'' Five years later, scientists found serotonin in brain extracts as well, and they soon learned that the recently invented hallucinogenic drug lysergic acid diethylamide worked by tapping into the brain's serotonin system and that if you took too much LSD you might end up wearing hair garlands and overusing the word ''wow.''

Serotonin and serotoninlike molecules have also been found throughout the animal, plant and fungal communities. As a vasoconstrictor, serotonin helps give a wasp sting its zing, and as a powerful hormone serotonin specifies the body plan of a sea urchin developing in its egg.

To synthesize their serotonin, humans and other species must start with tryptophan, an essential amino acid found in many dietary items, including turkey, cheese, tofu, nuts, seeds and bananas, a fruit that, despite its notorious comedic associations, always ends up on lists of ''very wholesome foods with possible medicinal value.''

Much effort has been devoted to the study of how serotonin operates in the brain, where it serves as a neurotransmitter, a chemical that activates brain cells to fire messages at each other through their impulsive Morse code. In the adult brain, all serotonin is supplied by a handful of cells located in the hindbrain, atop the spinal cord, but those neurons share their bounty widely through filamentous projections.

Not surprisingly, the serotonin signaling system is wondrously complex. Scientists have identified at least 15 distinct serotonin receptors, proteins that clasp onto serotonin and react accordingly. In addition, there is the serotonin transporter, a janitorial protein that removes the serotonin from the little cleft between nerve cells once the molecule's transmission task is through.

For all the intricacy, serotonin in the brain has a basic personality. ''It's a molecule involved in helping people cope with adversity, to not lose it, to keep going and try to sort everything out,'' said Philip J. Cowen, a serotonin expert at Oxford University and the Medical Research Council. In the fine phrase of his Manchester University colleague Bill Deakin, ''it's the 'Don't panic yet' neurotransmitter,'' said Dr. Cowen. Given serotonin's job description, disturbances in the system can contribute to depression, anxiety, panic attacks and mental calcification, an inability to see the world anew -- at least in otherwise vulnerable people.

Dr. Cowen emphasizes that serotonin disruption alone does not directly cause depression. Experiments have shown that if you shut down serotonin production in normal people by subjecting them to an extreme tryptophan-free diet, they may not notice the difference; those with a history of depression, however, may well fall back into their gloom.